Drugs for treating respiratory and nasal disorders are frequently administered in aerosol formulations through the mouth or nose. One widely used method for dispensing such aerosol drug formulations involves making a suspension formulation of the drug as a finely divided powder in a liquefied gas known as a propellant. The suspension is stored in a sealed container capable of withstanding the pressure required to maintain the propellant as a liquid. The suspension is dispensed by activation of a dose metering valve affixed to the container.
A metering valve may be designed to consistently release a fixed, predetermined mass of the drug formulation upon each activation. As the suspension is forced from the container through the dose metering valve by the high vapor pressure of the propellant, the propellant rapidly vaporizes, i.e., boils, leaving a fast moving cloud of very fine particles of the drug formulation. This cloud is usually directed into the nose or mouth of the patient by a channeling device, e.g., a cylinder like or cone-like passage, with one of its ends attached to the outlet of the pressurized container, and the other end inserted in the mouth or nose of the patient. Concurrently with the activation of the aerosol dose metering valve, the patient inhales the drug formulation particles into the lungs of nasal cavity. Systems for dispensing drugs in this way are known as "metered dose inhalers" (MDI's). See Peter Byron, Respiratory Drug Delivery, CRC Press, Boca Raton, Fla. 1990 for a general background on this form of therapy.
Patients often rely on medication delivered by MDI's for rapid treatment of respiratory disorders which are debilitating and, in some cases, even life threatening. Therefore, it is essential that the prescribed dose of aerosol medication delivered to the patient consistently meet the specifications claimed by the manufacturer and comply with the requirements set forth by drug regulatory authorities such as the FDA. Thus, testing of MDI units for proper drug delivery by the metering dose valve is a part of the manufacturer's quality assurance procedure.
One conventional method to test delivery of MDI's consists of taring each MDI and measuring the weight lost after the delivery of one dose. This method is accurate and adequate for testing a small number of samples. However, it is poorly suited for high speed production and packaging of MDI's.
A common method of testing drug delivery utilizes indirect pressure decay after activation of each MDI. This method does not render a direct mass measurement, but rather an approximation based upon the force exerted indirectly by the superheated vapor on a pressure transducer. As a consequence, this method is unable to detect MDI's which are marginally out of tolerance. Further, unacceptable inaccuracies result unless the production rate is less than about one and a half MDI's per second which is significantly below the optimal production rate. Therefore, multiple testing stations are used in the MDI production line leading to an increased maintenance burden and validation complications.
Thus, the manufacturer of MDI's is faced with a choice of i) testing each MDI and reducing the production speed to less than 1 and a half per second or ii) installing multiple testing machines in the production line. This dilemma has lead to a search for a method of accurately measuring the delivery of each MDI without sacrifice of production speed.